ABRAHAM M. SHANES l6l 



tion of potassium and exclusion of sodium are dependent on aerobic metabolism. 

 In the absence of oxygen glucose can supply additional energy to delay the 

 electrical and chemical changes, while the presence of iodoacetate, a well-known 

 inhibitor of glycolysis, accelerates these changes. A typical anesthetic agent, 

 cocaine, acts like glucose in counteracting the effects of oxygen lack, while 

 veratrine, which enhances excitability, at concentrations which have little 

 effect on ion distribution in oxygen, resembles the glycolytic inhibitor iodo- 

 acetate under anaerobic conditions. At still higher concentrations veratrine 

 acts like anoxia in its effect on E and ion movement, but the action differs 

 singularly from metabolic depression in at least two important respects: a) 

 unlike inhibition, veratrine effects can be completely counteracted by cocaine 

 and b) sodium is required in the external medium for potassium escape. These 

 observations and the well-known effects of veratrine on excitability (i8), 

 repetitive firing (58) and negative after-potentials (9) — which have not been 

 demonstrated for metabolic inhibition — make it unlikely that veratrine is 

 acting as an inhibitor. Indeed, respiration is enhanced by this alkaloid mixture 

 (40). The similarity of cocaine to glucose under anaerobic conditions is also 

 probably superficial; its many other effects on nerve functioning, as well as the 

 low concentration at which it is effective, suggest that it acts other than as a 

 substrate. 



The complete correlation between the resting potential and intracellular 

 potassium concentration, and the usual inverse relation between the potassium 

 and sodium shifts, must be stressed. If we accept this correlation of E and the 

 ionic shifts as a general principle, additional data available from experiments 

 on the action of metabolic inhibitors and substrates on the resting potential 

 may be considered to apply to the ions (53). Moreover, in recognition of the 

 dependence of nerve conduction and excitability on the state of polarization,^ 

 still more metabolic data are at hand. From these the following conclusions 

 may be drawn regarding the dependence of normal electrolyte distribution on 

 metabolism in frog nerve. 



a) Aerobic reactions are required; removal of O2 (2, 13, 17, 43, 53) or the 

 presence of cyanide (41), or of CO in the absence of light {t,?>), causes electrolyte 

 redistribution. Similar observations are now available for cephalopod axons, 

 where inhibitors of phosphorylations which leave oxygen consumption intact 

 are equally effective (22, 23). 



b) Anaerobic reactions contribute to a delay in the ionic shifts during anoxia; 



' For examj)le, in keeping with corresponding data for the polarization level, Feng (lo) 

 found that conduction block develops faster during anoxia in the presence of iodacetate and 

 that lactate counteracts iodoacetate block under aerobic conditions but not anaerobically. 

 This has been verified and extended by Lorente de No (34) and Fleckenstein (16). Conduction 

 block maj- be achieved without depolarization (i, 2, 16, 34), but the experimental conditions 

 from which we have drawn our data probably involve depolarization. 



